Sensitivity and specificity of intracoronary injection of acetylcholine for the induction of coronary artery spasm

Intracoronary injection of acetylcholine has been shown to induce coronary spasm in patients with variant angina. To examine its sensitivity and specificity, incremental doses of acetylcholine (20, 50 and 100 micrograms into the left coronary artery and 20 and 50 micrograms into the right coronary artery) were injected into the coronary artery or arteries in 70 patients with variant angina (Group 1) (mean age 57 years) and 93 patients without variant angina or angina at rest (Group 2) (mean age 54 years). Forty patients of the latter group had atypical chest pain, 16 cardiomyopathy, 14 arrhythmia, 11 valvular disease, 7 stable effort angina due to advanced coronary artery disease, 3 congenital heart disease and 2 hypertension. A temporary cardiac pacemaker set at 40 to 50 beats/min was positioned in the right ventricle. Coronary spasm was defined as total occlusion or severe vasoconstriction associated with chest pain or ischemic ST changes on the electrocardiogram or both. In Group 1, acetylcholine induced spasm in 63 (90%) of the 70 patients in the artery or arteries predicted to be responsible for spontaneous attacks. In Group 2, acetylcholine induced coronary spasm only in one patient with effort angina and advanced coronary artery disease although lesser degrees of vasoconstriction (less than or equal to 75% of the luminal diameter) occurred in most patients after acetylcholine (specificity of acetylcholine thus was 99%). In conclusion, intracoronary injection of acetylcholine is sensitive and reliable for the induction of coronary spasm.     

Induction of coronary arterial spasm by intracoronary administration of acetylcholine in patients with vasospastic angina

To examine whether intracoronary injections of acetylcholine induce coronary artery spasm in patients with vasospastic angina, incremental doses (20, 30 and 50 micrograms) were injected directly into the coronary arteries in 12 patients with variant angina (Group A: rest angina with electrocardiographic ST-segment elevation during attacks), 19 with vasospastic angina (Group B: rest angina and/or effort angina with variable threshold in the treadmill exercise stress test), 11 with organic coronary artery stenosis but without angina (Group C), and 14 without coronary artery disease (Group D). A temporary cardiac pacemaker was positioned in the right ventricle. Coronary artery spasm was defined as severe vasoconstriction (greater than or equal to 90% of reduction in the luminal diameter) with chest pain and/or ischemic changes in the electrocardiogram. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in all 12 patients (100%) of Group A, in 18 (95%) of Group B, in two (18%) of Group C, and in two (14%) of Group D. Thus, the sensitivity of this method for inducing coronary spasm was 100% in group A, 95% in Group B, and 97% in Group A plus Group B. The specificity for inducing spasm was 86% in Group D, and 84% in Group C and Group D. When acetylcholine was injected separately into the left and right coronary arteries, spasm of both the coronary arteries was observed in two (40%) of Group A, in five (33%) of Group B, and none (0%) of Group C and Group D. Acetylcholine (20 micrograms) induced coronary spasm in 10 (83%) of Group A and only in nine (47%) of Group B.(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of intracoronary injection of acetylcholine as a provocative test for coronary artery spasm in patients with vasospastic angina

Summary In order to examine both the sensitivity and specificity of coronary artery spasm induced by intracoronary injection of acetylcholine in patients with vasospastic angina, incremental doses of acetylcholine (20, 30, and 50 µg) were injected directly into each coronary artery in 21 patients with variant angina (group A), in 28 patients with other types of vasospastic angina (group B), and in 20 patients without any significant coronary artery disease (group C). Coronary artery spasm was defined as severe vasoconstriction (90% of reduction in luminal diameter) with chest pain and/or ischemic changes in the electrocardiogram. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in 20 patients (95%) of group A, in 27 patients (96%) of group B, and in only 2 patients (10%) of group C. The low dose of acetylcholine (20 µg) induced coronary spasm more frequently in group A patients (81%) than in group B patients (43%) (P<0.05). ST-segment elevation associated with anginal attacks was significantly (P<0.05) more frequent in group A (71%) than in group B (39%). When acetylcholine was injected separately into the left and right coronary arteries, spasm of both coronary arteries was observed in 7 out of 14 of group A (50%), in 8 out of 22 of group B (36%), and in none of the 20 of group C. We concluded that intracoronary injection of acetylcholine is a sensitive and reliable method for the induction of coronary spasm in patients with vasospastic angina as well as in those with variant angina.     

A study on coronary hemodynamics during acetylcholine-induced coronary spasm in patients with variant angina: endothelium-dependent dilation in the resistance vessels.

The epicardial coronary artery of patients with variant angina is hyperreactive to the constrictive effect of acetylcholine, but it is not known whether the coronary microvasculature also constricts in response to acetylcholine. Incremental doses of acetylcholine were injected into the left coronary artery of 57 patients with variant angina and with spasm in this artery. By measuring coronary sinus blood flow, coronary hemodynamic status just before angiographic documentation of spasm was examined. Acetylcholine induced spasm in the left coronary artery in all patients. It also decreased the diameter of the nonspasm artery by 36 +/- 19% from baseline. For all patients, coronary sinus blood flow was 89 +/- 38 ml/min at baseline and increased to 104 +/- 61 ml/min during an acetylcholine-induced anginal attack (p less than 0.01). In 10 patients with spasm in both the left anterior descending and left circumflex arteries (that is, multivessel spasm), coronary sinus blood flow decreased from 84 +/- 21 to 52 +/- 26 ml/min (p less than 0.01). In the other 47 patients with spasm in only one of these two arteries (that is, single-vessel spasm), coronary sinus blood flow increased from 90 +/- 41 to 115 +/- 61 ml/min (p less than 0.01) without change in the rate-pressure product. It is concluded that in patients with variant angina, acetylcholine induces spasm and constriction in the epicardial coronary artery, whereas it dilates the resistance vessels presumably through the release of the endothelium-dependent relaxing factor.     

Multivessel coronary spasm in patients with variant angina: a study with intracoronary injection of acetylcholine

Multivessel coronary spasm has been described but its incidence in patients with variant angina still remains unclear. Thirty-three patients with variant angina were studied during coronary angiographic examination with selective intracoronary injection of acetylcholine (ACh). In all but three patients, the location of ischemia during attack was determined by the electrocardiographic findings, by exercise 201Tl myocardial scintigraphy, and by two-dimensional echocardiography during a hyperventilation test, and the coronary artery (or arteries) responsible for the attack was predicted before the study. ACh induced spasm of at least one coronary artery in all but one patient. ACh induced spasm of both the left and right coronary arteries (i.e., multivessel coronary spasm) in 24 patients: in two of the four patients who were predicted to have spasm of the left coronary artery, in six of the 11 predicted to have spasm of the right coronary artery, in 13 of the 15 predicted to have spasm of both the left and right coronary arteries, and in three of the three in whom coronary artery responsible for attack had not been predicted. This ACh-induced spasm of the left and right coronary arteries occurred separately and no patients showed hemodynamic instability during attack. In one patient in whom multivessel coronary spasm had been predicted and ACh failed to induice coronary spasm, ergonovine maleate (0.2 mg) induced spasm of both the left and right coronary arteries simultaneously, resulting in severe prolonged hypotension. Nineteen of the 25 patients in whom multivessel coronary spasm was documented showed angiographically normal or nearly normal coronary arteries after administration of nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperventilation-induced simultaneous multivessel coronary spasm in patients with variant angina: an echocardiographic and arteriographic study

Left ventricular wall motion abnormalities during an attack of coronary spasm induced by hyperventilation were examined with use of two-dimensional echocardiography in 27 patients with variant angina. Transient abnormal wall motion (asynergy) confined to one coronary artery region was found in 18 of the 27 patients and transient abnormal motion extending over more than one coronary artery region in the remaining 9 patients. Spasm of more than one major coronary artery was demonstrated separately by coronary arteriography during an attack induced by injection of acetylcholine or ergonovine in seven of the nine patients who manifested asynergy in more than one coronary artery region. In one patient, spasm was demonstrated in one major coronary artery, and the other coronary arteries were severely stenosed or occluded organically. In the remaining patient, acetylcholine was not injected into both arteries; however, the attack was sometimes associated with ST segment elevation in the anterior leads and at other times in the inferior leads. Therefore, simultaneous multivessel coronary spasm seems to have occurred in eight of the nine patients who exhibited asynergy in more than one coronary artery region. The 8 patients with simultaneous multivessel coronary spasm had a higher degree and longer duration of ST segment elevation and a higher incidence of arrhythmias during the attack induced by hyperventilation than did the 19 patients with single vessel coronary spasm, and all of them had no significant organic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative sensitivity of intracoronary injection of acetylcholine for the induction of coronary spasm in patients with various types of angina pectoris

To elucidate the possible contribution of coronary artery spasm to the pathogenesis of angina pectoris, coronary arterial responses to intracoronary injection of acetylcholine were examined in patients with various types of angina pectoris. Coronary artery spasm with chest pain and/or electrocardiographic ischemic changes was angiographically demonstrated in 50 (85%) of 59 patients with angina pectoris. The sensitivity for coronary spasm was 92% (24 of 26) in patients with rest angina, 100% (16 of 16) in patients with both rest and effort angina, and 59% (10 of 17) in patients with effort angina, while it was only 6% (1 of 16) in patients without coronary artery disease. When patients with effort angina were subdivided according to the variability of anginal threshold for exertional angina, the sensitivity for coronary spasm was as high as 90% (9 out of 10) in patients with variable-threshold angina. In contrast, coronary spasm was less frequently (p less than 0.05) induced in patients with fixed-threshold angina (1 of 7, 14%). These results suggest that coronary arteries in patients with angina pectoris are quite susceptible to acetylcholine except in those patients with stable exercise tolerance or anginal threshold. Thus coronary artery spasm appears to play a significant role for the pathogenesis of angina pectoris in a large proportion of patients with effort angina as well as in patients with rest angina.     

Effects of intracoronary administration of nitroglycerin on contralateral intracoronary acetylcholine test results

This study examined the question of whether intracoronary administration of nitroglycerin modifies contralateral intracoronary acetylcholine test results. Acetylcholine was injected separately into both left and right coronary arteries in 63 patients with coronary spastic angina. Acetylcholine (20 and 50 μg) was injected first into the coronary artery responsible for the documented regional ischemia during spontaneous or induced attacks, and then into the other coronary artery. Coronary spasm was defined as severe transient coronary artery vasoconstriction with chest pain and/or electrocardiographic ischemic ST-segment deviation. Spasm was induced in either coronary artery in 60 patients (95%) and in both coronary arteries in 23 patients (37%). The frequency of induced spasm was 67% (42 of 63) in the coronary artery first challenged by acetylcholine. The coronary artery spasm subsided with the intracoronary injection of nitroglycerin (250-750 μg) in 19 patients. In the second challenge of intracoronary acetylcholine injection into the contralateral coronary artery, coronary spasm was induced in 29 (66%) of 44 patients. This was done without intracoronary administration of nitroglycerin in the first challenge and in 12 (63%) of 19 patients who had been given intracoronary nitroglycerin. The sensitivity for spasm induced by intracoronary acetylcholine appeared to be unaffected by nitro-glycerin. Coronary spasm with ST-segment elevation by intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary nitroglycerin (first: 89%, second: 26%, p > 0.05) as well as in those not receiving intracoronary nitroglycerin for the spasm in the first challenge (first: 52%, second: 13%, p > 0.05). Our results suggest that intracoronary nitroglycerin administered for prompt relief of coronary spasm exerts no significant influence on the results of the contralateral intracoronary acetylcholine test.     

Cardiac events in vasospastic angina: site and morphology of coronary artery spasm is related to the long-term prognosis of vasospastic angina

To determine whether the site and morphology of coronary artery spasm provoked with acetylcholine can predict the long-term prognosis of vasospastic angina, coronary artery spasm (more than 90% narrowing) provoked with acetylcholine was studied in 66 consecutive patients (56 males, 10 females, mean age 56 +/- 9 years) with vasospastic angina. All patients were followed for 6.7 +/- 0.9 years and the incidence of cardiac events such as sudden death, myocardial infarction or worsened unstable angina was compared with the site and morphology of provoked spasm. The site of spasm was regarded as proximal when spasm occurred in the proximal site of 3 major coronary arteries which was designated as segment 1, 6 or 11, according to the classification of the American Heart Association, and distal in other segments. The morphology of spasm was classified into 3 types, focal (12 cases, localized more than 90% narrowing with adjoining parts constricting less than 25%), diffuse (17 cases, diffuse more than 90% narrowing), and intermediate (37 cases, localized more than 90% narrowing with adjoining parts constricting 25-90%). The site of spasm was classified into 2 types, the proximal group (24 cases) and the distal group (42 cases). Cardiac events occurred in 7 patients during the follow-up period: sudden death in 2, myocardial infarction in 2, and worsened unstable angina in 3. As to the site of spasm, the incidence of cardiac events was 21% (5/24 patients) in the proximal group, significantly higher than 5% (2/42) in the distal group (p < 0.05). As to the site of spasm, the incidence of cardiac events was 41% (5/12) in the focal group, significantly higher than 3% (1/37) in the intermediate group and 6% (1/17) in the diffuse group (p < 0.001). The presence of proximal and focal coronary artery spasm was associated with a significantly higher incidence of cardiac events. The site and morphology of coronary artery spasm provoked with acetylcholine is related to the long-term prognosis of vasospastic angina.     

Effect of H1 receptor stimulation on coronary artery diameter in patients with variant angina: comparison with effect of acetylcholine

It has been suggested that histamine is involved in the pathogenesis of coronary spasm but its exact role remains unclear. H1 receptor stimulation of the coronary artery was performed with a selective intracoronary infusion of histamine (2 micrograms/min) in 21 patients with variant angina after blockade of the H2 receptor with cimetidine (25 mg/kg) and its effect on the coronary artery diameter was examined. Intracoronary injection of acetylcholine was also performed in 19 of the 21 patients. Ergonovine (0.2 mg) was intravenously administered in one patient. The coronary artery diameter was measured with cinevideodensitometric analysis. A mean plasma histamine concentration in the coronary sinus increased from 4 x 10(-9) to 7 x 10(-8) M 5 min after histamine infusion into the left coronary artery (n = 18). Coronary spasm was induced in 6 patients (29%) with histamine, in 18 (95%) with acetylcholine and in 1 with ergonovine. The effect of histamine on the luminal diameter was analyzed at the site of spasm in the 26 coronary arteries in which spasm was induced by acetylcholine or ergonovine. Of the 20 coronary arteries with a normal arteriogram or a fixed stenosis less than or equal to 50% of luminal diameter, histamine decreased the diameter in 4, increased it in 14 (70%) and caused no change in 2; of the 6 coronary arteries with a fixed stenosis greater than or equal to 75%, histamine decreased the diameter in 5 and increased it in 1. In the coronary arteries in which spasm was not induced by either acetylcholine or ergonovine, histamine increased the diameter, especially in those without advanced atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intracoronary injection of acetylcholine on coronary collateral circulation

To clarify the effect of intracoronary injection of acetylcholine on coronary collateral circulation, acetylcholine (20 and 50 μg) was injected directly into the donor artery of 5 patients with rest angina who had angiographically demonstrable collateral channels. Coronary spasm was defined as severe vasoconstriction (≥ 90% of luminal diameter) with chest pain and/or ischemic ST-segment changes. The intracoronary injection of acetylcholine induced spasm in all the 5 patients. The site of spasm was collateral vessels in 3, and the recipient coronary artery in 2 of the 5 patients. The spasm resolved spontaneously without administration of nitroglycerin. The contralateral intracoronary injection of acetylcholine also induced diffuse coronary spasm in 4 patients. These findings indicate that collateral vessels and recipient coronary arteries of the collateral circulation are susceptible to acetylcholine. Impaired relaxation and vasospastic responses to acetylcholine presumably due to endothelial dysfunction in the collateral and recipient coronary vessels may explain, at least in part, myocardial ischemia in patients with a well-developed collateral circulation. © 1993 Wiley-Liss, Inc.     

Clinical significance of plasma concentration of macrophage colony-stimulating factor in patients with vasospastic angina

OBJECTIVES: The concentration of macrophage colony-stimulating factor (M-CSF), an inflammatory cytokine, increases with the progression of coronary lesions, but no clinical investigations have evaluated the relationship to coronary vascular tone. The present study investigated the relationship between M-CSF and vasoreactivity of the coronary arteries in patients with vasospastic angina. METHODS: Vasospastic angina (VSA) was characterized by transient chest pain and ischemic ST segment changes at rest, or by a positive result in spasm provocation testing with acetylcholine. The subjects were 24 patients with stable VSA(inactive VSA group) treated on an outpatient basis, 31 VSA patients hospitalized with unstable angina (active VSA group), and 13 healthy subjects(control group). The sensitivity of determination of plasma M-CSF in blood was 40 pg/ml. The levels of this factor in each group were compared. Based on the findings of the acetylcholine vasospasm-induction test, patients were divided into those with single-vessel vasospasm and those with multivessel vasospasm, and, according to the dose of acetylcholine required to induce spasm, into high- and low-dose groups. Plasma M-CSF levels in each group were compared. RESULTS: Mean plasma M-CSF was 598 +/- 180 pg/ml in the inactive VSA group, 775 +/- 194 pg/ml in the active VSA group, and 632 +/- 103 pg/ml in the control group. The mean plasma M-CSF level in the active VSA group was significantly higher than that in the inactive VSA group(p < 0.01). Mean plasma M-CSF level in the single-vessel and multivessel vasospasm groups was highest for active VSA patients with multivessel vasospasm (872 +/- 173 pg/ml). The relationship with the acetylcholine induction dose clarified that plasma M-CSF levels were highest in patients with active VSA in the acetylcholine low-dose group (825 +/- 177 pg/ml, p < 0.001). CONCLUSIONS: Plasma M-CSF concentration reflects the vasoreactivity of coronary spasm in the VSA group, and may be an indicator of the severity of coronary endothelial dysfunction.     

Role of coronary artery spasm in ischemic heart disease. Therapeutic implications

The term coronary artery spasm should not be used interchangeably with the specific clinical syndrome "variant angina" since it does occur in other acute and chronic ischemic heart disease syndromes. The term coronary artery spasm should not be applied to patients with ischemic heart disease unless there is clinical, angiographic, and physiologic evidence of its presence. The diagnosis of coronary artery spasm is confirmed by angiography, i.e. change in caliber of the coronary arteries plus evidence of ischemia. Probable diagnosis is in patients who have the syndrome of variant angina, i.e. rest angina associated with ST segment elevation on the electrocardiogram. One can be highly suspicious that the spasm is at work in patients who have rest angina, especially those with unstable angina. One can be suspicious of patients who have variable effort angina or walk-through angina. Coronary artery spasm is a possibility in patients with an acute myocardial infarction or acute re-infarction and is also possible that sudden death in patients with normal coronary arteries can be related to coronary artery spasm. Coronary artery spasm is the usual cause of myocardial ischemia in patients with rest angina without effort angina. This has also commonly been documented in patients with rest and effort angina. There are isolated reports suggesting that patients with effort angina pectoris also develop coronary artery spasm. Coronary artery spasm has been documented to occur in association with acute myocardial infarction. Whether coronary artery spasm is the cause or the result of myocardial infarction has not been determined at this time. However, the recent combined use of intracoronary nitroglycerin and intracoronary streptokinase in patients with acute myocardial infarction has shown reversal of totally obstructed arteries and suggests the relationship between coronary artery disease, coronary artery spasm, and in situ coronary thrombosis. The incidence of sudden death in patients with documented coronary artery spasm is unknown. But, since complete heart block and/or ventricular tachycardia occur during episodes of coronary artery spasm, it is not unreasonable to assume that some patients have died as a result of these rhythm disturbances. The prognosis of patients with coronary artery spasm seems to depend on the presence or absence of severe coronary atherosclerosis, i.e. those with severe disease have a worse prognosis. Current therapy of patients with coronary artery spasm involves the use of nitrates and calcium antagonists.(ABSTRACT TRUNCATED AT 400 WORDS)     

Simultaneous multivessel coronary artery spasm demonstrated by quantitative analysis of thallium-201 single photon emission computed tomography

Thallium-201 myocardial scintigraphy with quantitative analysis of emission computed tomography was performed during episodes of angina in 19 patients with variant angina and nearly normal coronary arteriographic findings. Eleven patients (group I) were shown by arteriography to have spasm in 2 or more large coronary arteries. Eight patients (group II) had spasm in only 1 coronary artery. In 7 patients in group I, significant diffuse perfusion defects simultaneously appeared in multiple coronary artery regions on the scintigram (group IA). The extent and severity of the perfusion defect as measured by thallium-201 tomography were significantly greater in group IA than in group II (p less than 0.001 and p less than 0.01, respectively). The duration of transient ST-segment elevation during the attack in group IA was significantly longer than in group II (p less than 0.001). The incidence of ventricular arrhythmias, including ventricular tachycardia, or complete atrioventricular block during the anginal attack was significantly higher (p less than 0.05) in group IA than in group II. In all study patients, neither attack nor scintigraphic perfusion defect appeared on the repeat test after oral administration of nifedipine. In conclusion, multivessel coronary artery spasm simultaneously appears and causes the attack in many patients with variant angina and nearly normal coronary arteriographic findings, and myocardial ischemia due to simultaneous multivessel coronary spasm is likely to be more extensive and severe, persist longer and have a higher frequency of potentially dangerous arrhythmias than that due to spasm of only 1 coronary artery.     

Induction of coronary artery spasm by intracoronary acetylcholine: comparison with intracoronary ergonovine.

To investigate the mechanism of coronary spasm, we compared the action of acetylcholine with that of ergonovine in 11 patients with vasospastic angina (group 1) and in 15 patients with chest pain (group 2). Coronary arteriography was performed immediately after the patients received intracoronary injections of titrated increments of each agent. In the patients in group 1 occlusive or near-occlusive (99% luminal narrowing) coronary spasm associated with angina and ischemic electrocardiographic ST changes was noted in nine of 11 patients receiving acetylcholine and in all 11 patients receiving ergonovine. The region and the degree of the most severe coronary spasm on coronary arteriograms evoked by the two agents were the same in nine of the 11 patients in group 1. In the other two patients in group 1, spontaneous focal coronary spastic stenosis in the baseline coronary arteriogram was relieved by the intracoronary injection of acetylcholine, and a focal coronary occlusive spasm in the same region was induced repeatedly by the subsequent intracoronary injection of ergonovine (paradoxic phenomenon). In contrast, occlusive or near-occlusive coronary spasm was not induced by either agent in any patient in group 2. These results suggest that the two provocative tests for coronary spasm that involve acetylcholine and ergonovine are clinically useful in the diagnosis of vasospastic angina, but testing with intracoronary ergonovine is needed when a spontaneous focal coronary spasm is relieved by the intracoronary injection of acetylcholine. The results also indicate that in many patients with vasospastic angina, nonspecific hypersensitivity to acetylcholine or ergonovine in a definite region of the coronary arteries generally plays an important role in the induction of coronary spasm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multivessel coronary spasm as a cause of ischemic syncope in angina at rest

Two patients with vasospastic angina at rest developed ST segmentelevation both in the anterior and inferior leads during spontaneousand ergonovine-induced attacks. In both cases the acute myocardialischemia secondary to multivessel coronary spasm led to reversibleelectromechanical dissociation. Coronary arteriography showednormal coronary arteries in one case and severe three-vesseldisease in the other; spasm of the right coronary artery wasdemonstrated in both patients. These cases show that in patientswith vasospastic angina coronary spasm may simultaneously involvedifferent arteries and lead to ischemic electromechanical dissociation.Ergonovine testing is contraindicated in those patients withsuspected or proved multivessel coronary spasm.     

Diagnosis of multivessel coronary vasospasm by detecting postischemic regional left ventricular delayed relaxation on echocardiography using color kinesis.

BACKGROUND: It is not known whether multivessel coronary spasm occurs spontaneously in patients who have variant angina (VA) with demonstrated multivessel spasm induced by intracoronary injection of acetylcholine (ACh). Regional left ventricular (LV) diastolic dysfunction or wall motion abnormality may persist after an episode of coronary vasospasm. Color kinesis (CK) is a recent development that facilitates the echocardiographic evaluation of regional diastolic wall motion. METHODS AND RESULTS: Regional diastolic wall motion was evaluated using CK in 26 patients with VA within 1 week of the last episode of angina. The LV segmental filling fraction in the short-axis view during the first 30% of the diastolic filling time, expressed as a percentage, was used to objectively identify postischemic diastolic endocardial motion asynchrony. Diastolic asynchrony or regional LV delayed relaxation was noted in all 26 (100%) patients and in 14 (54%) it was detected in multiple vascular territories, suggesting multivessel spasm. Multivessel spasm was induced by ACh in 11 (79%) of the patients with suspected multivessel spasm by CK. In 11 (92%) of the 12 patients with multivessel spasm induced by ACh multiple regions of delayed relaxation had been noted by CK. The regions of delayed relaxation were largely consistent with the territories perfused by the arteries reacting to ACh (sensitivity: 96%, specificity: 91%). CONCLUSION: ACh induced spasm in the same coronary arteries as those perfusing the regions with delayed diastolic wall motion detected by CK in most of the patients with VA, suggesting that multivessel spasm does occur spontaneously in patients with susceptible arteries.     

Pathogenesis of unstable angina with 0- or 1-vessel disease. Important role of coronary artery spasm.

In order to examine the possible role of coronary artery spasm in the pathogenesis of unstable angina, provocative testing for coronary spasm was performed in 43 patients with unstable angina who had 0- or 1-vessel disease. Coronary spasm was induced in 20 (65%) of 31 patients by hyperventilation testing (ST increases in 18, ST decreases in 2). Anginal attacks with either ST-segment elevation or ST-segment depression in patients without a significant organic stenosis were induced in 23 (55%) of 42 patients during treadmill exercise testing. Coronary artery spasm, showing severe (> or = 90%) vasoconstriction with angina and/or ischemic electrocardiographic ST-segment deviation, was also documented angiographically in 42 (98%) of 43 patients following intracoronary injection of acetylcholine. We conclude that dynamic coronary obstruction plays an important role in the genesis of attacks in patients with unstable angina who had 0- or 1-vessel organic coronary artery disease.     

Angiographic demonstration of spontaneous diffuse three vessel coronary artery spasm

The spontaneous occurrence of diffuse three vessel coronary artery spasm was documented during routine coronary angiography in three patients with a history of variant angina. Quantitative angiographic analysis of 18 arterial segments demonstrated that the mean luminal diameter of 1.47 mm during spasm increased to 2.47 mm after the administration of nitroglycerin (p less than 0.0001). The underlying coronary arteries were normal or near normal. Although multivessel spasm has previously been considered to be uncommon and its spontaneous occurrence during angiography only rarely documented, these cases suggest that it may be more common than previously recognized. In addition to important diagnostic considerations, this phenomenon may have important implications regarding the pathophysiologic role of endothelium in coronary artery spasm.     

Induction of coronary artery spasm by acetylcholine in patients with variant angina: possible role of the parasympathetic nervous system in the pathogenesis of coronary artery spasm

We injected acetylcholine (ACh), the neurotransmitter of the parasympathetic nervous system, into the coronary arteries of 28 patients with variant angina. Injection of 10 to 80 micrograms ACh into the coronary artery responsible for the attack induced spasm together with chest pain and ST segment elevation or depression on the electrocardiogram in 30 of the 32 arteries of the 25 of the 27 patients. The injection of 20 to 100 micrograms ACh into the coronary artery not responsible for the attack in 18 patients resulted in various degrees of constriction in most of them, but no spasm in any of them. After intravenous injection of 1.0 to 1.5 mg atropine sulfate, the injection of ACh into the coronary artery responsible for the attack did not induce spasm or attack in any of the nine coronary arteries injected in eight patients. We conclude that the intracoronary injection of ACh induces coronary spasm and attack in patients with variant angina and that the activity of the parasympathetic nervous system may play a role in the pathogenesis of coronary spasm. We also conclude that the intracoronary injection of ACh is a useful test for provocation of coronary spasm.